Phage-mediated transmission of colistin resistance in Acinetobacter baumannii

Abstract

Abstract Antimicrobial resistance is a global threat to human health, and Acinetobacter baumannii is a paradigmatic example of how rapidly bacteria become resistant to clinically relevant antimicrobials. The emergence of multidrug-resistant A. baumannii strains has forced the revival of colistin as a “last-resort” drug, suddenly leading to the emergence of colistin resistance. Here, we demonstrate that the A. baumannii temperate bacteriophage Φ19606 acts as a vehicle of colistin resistance through the horizontal transfer of the eptA1 gene, encoding a lipid A phosphoethanolamine transferase which prevents colistin from binding to the outer membrane. eptA1 is coregulated with its chromosomal homolog pmrC via the PmrAB two-component system, and the expression of both genes is induced by low calcium and magnesium levels, resulting in colistin resistance. Moreover, eptA1 facilitates the emergence of spontaneous colistin-resistant mutants. Overall, Φ19606 is an unprecedented example of a self-transmissible phage vector implicated in the dissemination of colistin resistance.